Analytical method, changes stability

In the case where a method change is deemed annual reportable or even as a CBE supplement, implementation can be immediate with perhaps a crossover at the next time point for ongoing smdies. In this instance, new studies could be initiated using the new method. Table 5.4 lists some of the typical specification/analytical method changes and potential impact on stability studies. 

A variety of analytical methods, such as ELISA and HPLC, can be used to evaluate the effect of excipients or lyophilization on the stability of the biophar-maceutical product. Some parameters the analytical methods should evaluate are degradation, chemical and physical changes, aggregation, adsorption, and loss of biological activity. 

All stability studies on clinical trial materials must be carried out in full accordance with cGMPs, even if a research department carries out the studies. All studies must be carried out by adequately trained personnel under adequate work conditions. The personnel must use properly qualified and calibrated stability chambers, instruments, reagents, and standards. They must follow validated analytical methods and approved written procedures, and they must properly document all work. There must be proper sample and data traceability, change control, and go on. 

If the development report does not contain information about changes to the formulation, critical processes, analytical methods and assays, equipment, stability, and so forth, there is alow probability that what has been prepared will be useful to the FDA investigator(s) or the firm during an inspection. 

One source of prediction error is the inherent accuracy and precision of the reference analytical method used. If the reference method produces erroneous values that are consistently high or low, this bias will be reflected in the prediction results. Other sources of prediction error relate to the reproducibility, stability, and repeatability of the NIR instrument. Reproducibility (precision) is validated by making repeated measurements of the same sample and removing it between runs. Small changes in conditions may occur owing to multiple insertions of a sample onto the instrument. Stability refers to similar changes that may occur over... 

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